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<!doctype html>
<html lang="en">
<head>
<meta charset="utf-8">
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<title>Presentation</title>
<meta name="description" content="BI281H Discussion">
<meta name="author" content="Michael J. Harms">
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<div class="reveal">
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<div class="slides">
<section>
<h2>The Citric Acid Cycle is a Roundabout</p>
<h4>2017-11-15</h4>
<br/>
</section>
<section>
<h4>Conceptual goals</h4>
<ul>
<li class="fragment">Understand how the pathways we've discussed thus far tie into the rest of metabolism</li>
<li class="fragment">Understand that most metabolites can be converted into one another by running through central metabolic pathways and intermediates</p>
</ul>
<h4>Skill goals</h4>
<ul>
<li class="fragment">Reason about metabolic energy extraction</li>
<li class="fragment">Reason about metabolic pathway regulation</li>
</ul>
</section>
<section>
<img src="presentation-data/22/img/overview.png" height="35%" width="35%"/>
</section>
<section>
<p>Citric Acid Cycle</p>
<img src="presentation-data/22/img/tca.png" height="55%" width="55%" />
</section>
<section>
<p>True or False</p>
<p>The citric acid cycle is reduces carbons</p>
<p class="fragment" style="color:blue">False. </p>
<p class="fragment">So what does it reduce?</p>
<p class="fragment" style="color:blue">$NAD^{+} + H^{-} \rightarrow NADH$ and $Q + H^{+} + H^{-} \rightarrow QH_{2}$</p>
</section>
<section>
<p>Which allows cells to extract more energy, glycolysis or the citric acid cycle?</p>
<p class="fragment" style="color:blue">The citric acid cycle (yields ~30 ATP/glucose relative to 2 for glycolysis)</p>
<p class="fragment">Why is its yield so much higher?</p>
<p class="fragment" style="color:blue">It fully oxidizes glucose to $CO_{2}$</p>
</section>
<section>
<p>Citric acid cyle summary</p>
<ul>
<li class="fragment">It's used for carbon oxidation</li>
<li class="fragment">The reduced products it generates ($NADH$ and $QH_{2}$) can be oxidized by oxidative phosphorylation to yield $ATP$</li>
<li class="fragment">Provides access to much higher energy yields for glucose than glycolysis...provided there is some "final $e^{-}$ acceptor" around.</li>
<li class="fragment">Generates useful intermediates used throughout metabolism</li>
<li class="fragment">It's a buffer for metabolites that assures a steady concentration of important precursor molecules</li>
</ul>
</section>
<section>
<p>A "roundabout" is a good mental picture of the citric acid cycle</p>
<img src="presentation-data/23/img/roundabout.png" />
</section>
<section>
<p>The citric acid cycle acts as a "buffer" for all metabolism</p>
<div class="row">
<div class="col-xs-6">
<img src="presentation-data/22/img/anabolic-tca.png" height="150%" width="150%" />
</div>
<div class="col-xs-6">
<img src="presentation-data/22/img/incoming-tca.png" height="150%" width="150%" />
</div>
</div>
</section>
<section>
<p>Citric acid cycle is <em>central</em> to all metabolism</p>
<img src="presentation-data/21/img/roche-metabolic_pathways_small.png" />
</section>
<section>
<p>Key points</p>
<ul>
<li class="fragment">The citric acid cycle can "buffer" metabolism by allowing free interchange between a vast number of metabolites</li>
<li class="fragment">Metabolism is built on a key set of "core" metabolites (such as pyruvate, acetyl-coA and $\alpha$-ketoglutarate)</li>
<li class="fragment">The citric acid cycle changes rates, but never turns off because of its role as a central "roundabout" in metabolism</li>
</ul>
<p class="fragment"><span style="color:red">IMPORTANT:</span> Do not worry about (or get lost in) details that follow. Focus on the key points and how these examples <em>illustrate</em> these points.</p>
</section>
<section data-transition="fade">
<p>Most of our energy comes from three forms of fuel</p>
<ul>
<li>Sugar</li>
<li>Fat</li>
<li>Protein</li>
</ul>
</section>
<section data-transition="fade">
<p>Most of our energy comes from three forms of fuel</p>
<ul>
<li style="color:red">Sugar</li>
<li>Fat</li>
<li>Protein</li>
</ul>
</section>
<section>
<p>Sugar</p>
<img src="presentation-data/23/img/sugar-complexity.png" height="40%" width="40%" />
</section>
<section>
<p>Most of our energy comes from three forms of fuel</p>
<ul>
<li>Sugar</li>
<li style="color:red">Fat</li>
<li>Protein</li>
</ul>
</section>
<section>
<p>Fat is broken into a glycerol molecule and its acyl chains</p>
<img src="presentation-data/23/img/fat-0.png" height="80%" width="80%" />
</section>
<section>
<p>Glycerol is converted to dihydroxyacetone phosphate</p>
<p class="fragment">Sound familiar? <span class="fragment" style="color:blue">It's a glycolysis intermediate</span></p>
</section>
<section>
<p>Acyl chains are "activated" using conezyme A</p>
<img src="presentation-data/23/img/fat-1.png" height="65%" width="65%" />
</section>
<section>
<p>Coenzyme A (coA) acts as a "handle" for cells to move around actetate in both catabolism and anabolism</p>
<img src="presentation-data/22/img/coash.png" height="75%" width="75%" />
</section>
<section>
<p>2 carbon units are sequentially chopped off</p>
<img src="presentation-data/23/img/fat-2.png" height="55%" width="55%" />
</section>
<section>
<p>Is the conversion of an acyl chain to acetyl-coA an oxidation or reduction?</p>
<p class="fragment" style="color:blue">Oxidation.</p>
<p>So what other reaction might be coupled to this one?</p>
<p class="fragment" style="color:blue">Each round generates 1 $QH_{2}$ and 1 $NADH$</p>
</section>
<section>
<p>Fatty acid oxidation produces an acetyl-coA molecule for every two carbons in the acyl chain</p>
<p>What happens to the acetyl-coA?</p>
<p class="fragment" style="color:blue">It enters the citric acid cycle (where it yields 3 $NADH$, 1 $QH_{2}$ and 1 $GTP$)</p>
</section>
<section>
<p>Fats store a lot of energy</p>
<p class="fragment">"Typical" triglyceride will have 3 acyl chains of 16 carbons</p>
<p class="fragment">If you add up reduced $NADH$ and friends you get $\frac {13 \ ATP}{2 \ carbons}$</p>
<p class="fragment">Total yield is $3 \ chains \times \frac{16\ carbons}{chain} \times \frac{13\ ATP}{2 \ carbons}$</p>
<p class="fragment">$3 \times 16 \times 13/2 = 312 \ ATP$</p>
</section>
<section>
<p>Fats have higher $ATP$ yield per carbon than glucose</p>
<p>Fat: $312/48 = 6.5 ATP \cdot carbon^{-1}$</p>
<p>Glucose: $32/6 = 5.3 ATP \cdot carbon^{-1}$</p>
<p class="fragment"><em>Why is this the case?</em></p>
<p class="fragment" style="color:blue">Glucose is already oxidized relative to an acyl chain</p>
<p class="fragment">Gram per gram, fat has twice as much stored energy as sugar</p>
</section>
<section>
<p>Fats can be synthesized starting from acetyl-coA, just like glucose can be synthesized from pyruvate by gluconeogenesis</p>
<p class="fragment">Do you think this is a simple reversal of $\beta$-oxidation? Why or why not?</p>
<p class="fragment" style="color:blue">No. Just like gluconeogenesis, irreversible steps must be bypassed.</p>
</section>
<section>
<p>Big idea:</p>
<p>There are lots of steps in fatty acid oxidation, but those steps all work to convert the material into the same bits that we saw sugar become ($DHAP$, $acetyl-coA$, $NADH$, $QH_{2}$)</p>
</section>
<section>
<p>Most of our energy comes from three forms of fuel</p>
<ul>
<li>Sugar</li>
<li>Fat</li>
<li style="color:red">Protein</li>
</ul>
</section>
<section>
<p>How do you think cells deal with the complex structure and chemistry of proteins?</p>
<p class="fragment" style="color:blue">They unfold the protein and chop it up into amino acids with proteases</p>
</section>
<section>
<p>Free amino acids can be directly recycled to make more proteins</p>
<p class="fragment">They can also be used for fuel or to make other biomolecules</p>
</section>
<section>
<p>Many amino acids can be directly converted to things like pyruvate or acetyl-coA</p>
<img src="presentation-data/23/img/protein-0.png" height="45%" width="45%" />
<img src="presentation-data/23/img/protein-1.png" height="45%" width="45%" />
<img src="presentation-data/23/img/protein-2.png" height="85%" width="85%" />
</section>
<section>
<p>Nitrogens get passed around a lot via <em>transamination</em></p>
<p>$\alpha$-ketoglutarate can be combined with glutamine to make 2 glutamates</p>
<img src="presentation-data/23/img/protein-3.png" height="85%" width="85%" />
<p>Recognize $\alpha$-ketoglutarate? <span class="fragment" style="color:blue">Citric acid cycle intermediate</span></p>
</section>
<section>
<p>Glutamate and pyruvate can be converted to $\alpha$-ketoglutarate and alanine</p>
<img src="presentation-data/23/img/protein-4.png" height="85%" width="85%" />
</section>
<section>
<p>Amino acid catabolism is intimately tied into the citric acid cycle</p>
<img src="presentation-data/23/img/protein-5.png" height="70%" width="70%" />
</section>
<section>
<p>Amino acids are made by many inter-conversions between amino acids and other metabolites...in their own metabolic cycles</p>
<img src="presentation-data/23/img/protein-6.png" height="90%" width="90%" />
</section>
<section>
<p>Key point: a dizzying array of molecules are made and processed in cells, but are tied together through several key metabolites.</p>
<img src="presentation-data/21/img/roche-metabolic_pathways_small.png" />
</section>
<section>
<p>Summary</p>
<ul>
<li class="fragment">Most metabolism ties directly into the citric acid cycle or glycolysis via a set of "core" metabolites (such as pyruvate, acetyl-coA and $\alpha$-ketoglutarate)</li>
<li class="fragment">This allows cells to shift metabolites around to control processes in a coordinated fashion</li>
<li class="fragment">The citric acid cycle changes rates, but never turns off because of its role as a central "roundabout" in metabolism</li>
</ul>
</section>
</div>
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